Introduction

Chapter
Part of the Nutrition and Health book series (NH)

Abstract

Scientific discoveries and advances often negate or disprove what we previously thought or at least give us a better understanding of the topic under consideration. The emergence of the health benefits of nitrite and nitrate in the proper context negates or counters the more than 50 years of research implicating these two anions as toxic, unwanted food additives that potentially cause cancer. New research has revealed that dietary nitrate, primarily from green leafy vegetables, can be serially reduced to nitrite and to nitric oxide. This new paradigm is now recognized as a redundant system for endogenous nitric oxide-based signaling that perhaps can overcome or compensate for loss of nitric oxide synthase production of NO. Understanding how nitrate and nitrite can be metabolized to NO while preventing formation of low molecular weight N-nitrosamines will allow for safe and effective dietary and/or therapeutic strategies to restore endogenous NO-based signaling.

Keywords

Food Nutrition Nitric oxide Nitrite Nitrate Diet 

References

  1. 1.
    Vita JA, Keaney Jr JF. Endothelial function: a barometer for cardiovascular risk? Circulation. 2002;106(6):640–2.CrossRefPubMedGoogle Scholar
  2. 2.
    Vita JA, et al. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation. 1990;81(2):491–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Garthwaite J, Charles SL, Chess-Williams R. Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature. 1988;336(6197):385–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Stuehr DJ, Marletta MA. Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc Natl Acad Sci U S A. 1985;82(22):7738–42.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Doherty DH, et al. Rate of reaction with nitric oxide determines the hypertensive effect of cell-free hemoglobin. Nat Biotechnol. 1998;16(7):672–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Dou Y, et al. Myoglobin as a model system for designing heme protein based blood substitutes. Biophys Chem. 2002;98(1–2):127–48.CrossRefPubMedGoogle Scholar
  7. 7.
    Gladwin MT, et al. Relative role of heme nitrosylation and beta-cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulation. Proc Natl Acad Sci U S A. 2000;97(18):9943–8.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Shiva S, et al. Ceruloplasmin is a NO oxidase and nitrite synthase that determines endocrine NO homeostasis. Nat Chem Biol. 2006;2(9):486–93.CrossRefPubMedGoogle Scholar
  9. 9.
    Moncada S, Higgs A. The L-arginine nitric oxide pathway. N Engl J Med. 1993;329(27):2002–12.Google Scholar
  10. 10.
    Kleinbongard P, et al. Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. Free Radic Biol Med. 2006;40(2):295–302.CrossRefPubMedGoogle Scholar
  11. 11.
    Lundberg JO, Weitzberg E, Gladwin MT. The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov. 2008;7(2):156–67.CrossRefPubMedGoogle Scholar
  12. 12.
    Hord NG, Tang Y, Bryan NS. Food sources of nitrates and nitrites: the physiologic context for potential health benefits. Am J Clin Nutr. 2009;90(1):1–10.CrossRefPubMedGoogle Scholar
  13. 13.
    Crawford JH, et al. Transduction of NO-bioactivity by the red blood cell in sepsis: novel mechanisms of vasodilation during acute inflammatory disease. Blood. 2004;104(5):1375–82.CrossRefPubMedGoogle Scholar
  14. 14.
    Jungersten L, et al. Both physical fitness and acute exercise regulate nitric oxide formation in healthy humans. J Appl Physiol. 1997;82(3):760–4.PubMedGoogle Scholar
  15. 15.
    Lundberg JO, et al. Nitrate and nitrite in biology, nutrition and therapeutics. Nat Chem Biol. 2009;5(12):865–9.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Benjamin N, et al. Stomach NO synthesis. Nature. 1994;368(6471):502.CrossRefPubMedGoogle Scholar
  17. 17.
    Lundberg JO, et al. Intragastric nitric oxide production in humans: measurements in expelled air. Gut. 1994;35(11):1543–6.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Lundberg JO, et al. Nitrate, bacteria and human health. Nat Rev Microbiol. 2004;2(7):593–602.CrossRefPubMedGoogle Scholar
  19. 19.
    Spiegelhalder B, Eisenbrand G, Preussman R. Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds. Food Cosmet Toxicol. 1976;14:545–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Govoni M, et al. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash. Nitric Oxide. 2008;19(4):333–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Duncan C, et al. Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate [see comments]. Nat Med. 1995;1(6):546–51.CrossRefPubMedGoogle Scholar
  22. 22.
    Björne HH, et al. Nitrite in saliva increases gastric mucosal blood flow and mucus thickness. J Clin Invest. 2004;113(1):106–14.CrossRefPubMedCentralGoogle Scholar
  23. 23.
    Jansson EA, et al. Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate. Free Radic Biol Med. 2007;42(4):510–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Petersson J, et al. Dietary nitrate increases gastric mucosal blood flow and mucosal defense. Am J Physiol Gastrointest Liver Physiol. 2007;292(3):G718–24.CrossRefPubMedGoogle Scholar
  25. 25.
    Miyoshi M, et al. Dietary nitrate inhibits stress-induced gastric mucosal injury in the rat. Free Radic Res. 2003;37(1):85–90.CrossRefPubMedGoogle Scholar
  26. 26.
    Björne HH, Weitzberg E, Lundberg JO. Intragastric generation of antimicrobial nitrogen oxides from saliva—physiological and therapeutic considerations. Free Radic Biol Med. 2006;41(9):1404–12.Google Scholar
  27. 27.
    Lundberg JO, Govoni M. Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic Biol Med. 2004;37(3):395–400.CrossRefPubMedGoogle Scholar
  28. 28.
    Bryan NS. Nitrite in nitric oxide biology: cause or consequence? A systems-based review. Free Radic Biol Med. 2006;41(5):691–701.CrossRefPubMedGoogle Scholar
  29. 29.
    van Faassen EE, et al. Nitrite as regulator of hypoxic signaling in mammalian physiology. Med Res Rev. 2009;29(5):683–741.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Lundberg JO, Weitzberg E. NO generation from nitrite and its role in vascular control. Arterioscler Thromb Vasc Biol. 2005;25(5):915–22.CrossRefPubMedGoogle Scholar
  31. 31.
    Dykhuizen RS, et al. Antimicrobial effect of acidified nitrite on gut pathogens: importance of dietary nitrate in host defense. Antimicrob Agents Chemother. 1996;40(6):1422–5.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Duncan C, et al. Protection against oral and gastrointestinal diseases: importance of dietary nitrate intake, oral nitrate reduction and enterosalivary nitrate circulation. Comp Biochem Physiol A Physiol. 1997;118(4):939–48.CrossRefPubMedGoogle Scholar
  33. 33.
    Weitzberg E, Lundberg JO. Nonenzymatic nitric oxide production in humans. Nitric Oxide. 1998;2(1):1–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Larauche M, et al. Protective effect of dietary nitrate on experimental gastritis in rats. Br J Nutr. 2003;89(6):777–86.CrossRefPubMedGoogle Scholar
  35. 35.
    Larauche M, Bueno L, Fioramonti J. Effect of dietary nitric oxide on gastric mucosal mast cells in absence or presence of an experimental gastritis in rats. Life Sci. 2003;73(12):1505–16.CrossRefPubMedGoogle Scholar
  36. 36.
    Sobko T, et al. Gastrointestinal nitric oxide generation in germ-free and conventional rats. Am J Physiol Gastrointest Liver Physiol. 2004;287(5):G993–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Bryan NS, Ivy JL. Inorganic nitrite and nitrate: evidence to support consideration as dietary nutrients. Nutr Res. 2015;35(8):643–54.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Molecular and Human GeneticsBaylor College of Medicine, Molecular and Human GeneticsHoustonUSA
  2. 2.Department of MedicineHarvard Medical SchoolBostonUSA
  3. 3.Department of MedicineBrigham and Women’s HospitalBostonUSA

Personalised recommendations